Human poly (A) binding protein (PABP) is an evolutionarily conservative nucleotide binding domain and an important eukaryotic RNA binding protein. It is highly conservative and regulates translation initiation, mRNA stability and also the length of poly (A) tail in polyadenylation reaction, and must be blocked by messenger ribonucleoprotein (mRNP) during early embryogenesis. PABP functions as an important regulator in gene expression by controlling translation initiation.
Grange T. et al. cloned the cDNA of Human poly (A) binding protein (PABP) in 1999. It is a new member of terminal oligo pyramine protein family. Members of the family have an oligo pyridine in their 5′-terminus and encode complexes involved in translation, especially in translation control of developmental regulation. PABP gene has 15 exons whose total length is 2.86 kb, and 14 introns of the length 22 kb. 5′-UTR of human PBRP consists of 505 nucleotides which is far longer than the average length (44+/−4) of those of other vertebrates, which indicates it may have other regulation functions. There is an A rich region in human PABP gene from 73 to 123 bp, which participates in repression of PABP translation, and PABP may self-regulate its expression by binding the 5′-UTR. Developmental-dependent translation regulation of PABP mRNA is often associated to oligo pyridine in its 5′ terminus. Replacement of the cytosine in its capped site by a purine leads to loss of its translation regulation function. That cytosine and nearly 30 nucleotides around it form a complex which encodes many translation related proteins such as ribosomal proteins, elongation factors 1α and 2 (EF1α and EF2), and involved in cis-mediated regulation of developmental-dependent translation by translation factors. Transcription of PABP gene usually begins from one or two cytosine in oligo pyridine chain and its mRNA is 29 kb. Its translation product is a 70,244 dalton protein. Human PABP is highly homologous to yeast PABP at the N-terminus and has relatively high level of poly (A) binding activity (Nucl. Aci. Res, 1987, 15 (12): 4771–4787). Number of the repeating subunits composed of nearly 80 amino acids is four times that of other nucleotide binding proteins. Its C-terminus is also similar to that of its yeast homolog, having 150 amino acid sequence and rich in proline, alanine, and glutamic acid, which amount for a very high percentage of about 48% of all amino acid sequence (J. Biol. C., 1999, 274 (3), 1708–1714).
Novel polypeptide of the present invention shares 86% homology and 94% similarity at the protein level with the known human poly (A) binding protein, and they also have similar structural characteristics, molecular weight, isoelectric point and peptide map. Thus this polypeptide is thought to be a component of an novel human poly (A) binding protein and named “human poly (A) binding protein 20.13,” which has similar biological functions of the known protein, including protein translation regulation and RNA stability. Overexpression of this polypeptide will cause developmental abnormality. Besides, it can be used in diagnosis and treatment of related diseases.
As above-described human polyadenylation binding Protein 20.13 plays an essential role in the regulation of important biological functions such as cell division and embryogenesis, and it is believed that lots of proteins are involved in these regulations. So the determination of those related human polyadenylation binding Protein 20.13 of actin-binding proteins, especially of their amino acid sequences is always desired in this field. The isolation of this novel human polyadenylation binding Protein 20.13 builds the basis for research of the protein function under normal and clinical conditions and this protein can be the basis of disease diagnosis and/or drug development. So the isolation of its cDNA is very important.